Congestive heart failure (CHF) may be considered a condition in which cardiac output is not adequate to meet the metabolic needs of the body, either at rest or with exercise, usually accompanied by an increase in cardiac filling pressure and/or volume. Implicit in that physiological definition is that CHF can be caused by an abnormality in systolic function leading to a defect in expulsion of the blood (systolic HF), or by an abnormality in diastolic function leading to a defect in ventricular filling (diastolic HF).
Patients suffering from systolic heart failure (SHF) typically exhibit reduced or weakened pumping action of the heart, and is characterized by impaired ventricular contraction, most likely due to changes in the signal transduction mechanisms regulating cardiac excitation-contraction coupling. The result is a decrease in stroke volume and a compensatory rise in preload (often measured as ventricular end-diastolic pressure or pulmonary capillary wedge pressure). A common clinical measurement is the ejection fraction (EF). The ejection fraction is a calculation of how much blood is ejected out of the left ventricle (stroke volume), divided by the maximum volume remaining in the left ventricle at the end of diastole or relaxation phase. A normal ejection fraction is greater than 50%. Systolic heart failure has a decreased ejection fraction of less than 50%.
Because the ventricle is inadequately emptied, ventricular end-diastolic pressure and volumes increase. This is transmitted to the atrium. On the left side of the heart, the increased pressure is transmitted to the pulmonary vasculature, and the resultant hydrostatic pressure favors extravassation of fluid into the lung parenchyma, causing pulmonary edema. On the right side of the heart, the increased pressure is transmitted to the systemic venous circulation and systemic capillary beds, favoring extravassation of fluid into the tissues of target organs and extremities, resulting in dependent peripheral edema. Progressive worsening of heart failure can lead to cardiogenic shock, arrhythmias, electromechanical dissociation, and death.
Many SHF patients are treated with drugs, including those drugs designed for the purpose of directly stimulating cardiac tissue in order to increase contractility. However, drugs have possible undesirable side effects, and drugs do not always work for their intended purpose. There have also been a number of device therapies investigated.
Additional therapies have focused on the role that nitric oxide (NO) may play in heart failure. NO is a diffusible highly reactive gas formed by three NO synthase (NOS) isoforms: neuoronol, inducible, and endothelial. NO is produced by the vascular endothelium and serves to promote vascular homeostatis. It has been hypothesized that endothelial nitric oxide synthase (eNOS) in the left ventricle is decreased in instances of SHF, and neuronal nitric oxide synthase (nNos) and inducible nitric oxide synthase (iNOS) in the left ventricle are increased in instances of SHF. Further, cardiac β-adrenergic receptor (β-AR) signaling is impaired leading to desensitization of the myocardium to catecholamines.
Given the high incidence of SHF with left ventricular dysfunction, additional devices and methods of treatment would be desirable.